CONCLUSION The different microalgae extracts, particularly the ethanolic extract ofC. reinhardtii, are promising potential candidates for the development of future natural antichagasic drugs. Keratinocyte proliferation serves as a crucial process in skin wound healing. The zinc-sensing G-protein coupled receptor 39 (GPR39), which is highly expressed in keratinocytes, has been shown to promote skin wound healing. The aim of this study was to investigate the effect of GPR39 activation on proliferation of keratinocytes and its underlying mechanism using immortalized human keratinocytes (HaCaT) as an in vitro model. GPR39 was functionally expressed in HaCaT cells. BrdU proliferation assays showed that treatment with GPR39 agonist TC-G 1008 (100 nM and 1 μM) increased cell proliferation. TC-G 1008 also enhanced ERK phosphorylation in time- and concentration-dependent manners. This effect was suppressed by co-treatment with wortmannin (PI3K inhibitor) and U0126 (MKK inhibitor). Of note, neither inhibition of Gαq-phospholipase C (PLC)-[Ca2+]i nor Gαs-PKA pathway affected GPR39 stimulation-induced ERK phosphorylation. https://www.selleckchem.com/products/Etopophos.html Similarly, barbadin, an inhibitor of G-protein-independent β-arrestin pathway, did not suppress ERK phosphorylation induced by GPR39 activation. Of particular importance, wortmannin, U0126, and FR180204 (ERK inhibitor) abrogated the effect of TC-G 1008-induced cell proliferation. Taken together, this study reveals novel insights into the role of GPR39 in regulating keratinocyte proliferation via a PI3K-MKK-ERK-dependent mechanism. GPR39 agonists may be used in enhancing keratinocyte proliferation, which may be beneficial for the cutaneous wound treatment. BACKGROUND Heat stroke-induced mortality is rising across the globe. So, the design of prophylactic and/or therapeutic modalities for heat stroke is pressing need. The common plant derived flavonoid exhibits strong anti-oxidant and anti-inflammatory activities; however, its effects in heat stroke remain unknown. The study aimed to investigate the cardioprotective effects of myricetin on heat stroke induced acute myocardial injury as well as lethality in rats and to explore the underlying mechanisms. METHODS Myocardial injury was induced by subjecting the anesthetized rats to a high ambient temperature of 43 °C for 70 min. An intragastrical dose of myricetin (5-25 mg/kg body weight) was given to rats once per day for one week prior to the start of heat stress. Heat shock protein 72 antibodies was given intraperitoneally to rats 24 h before the start of heat stress. Myocardial injury severity was estimated by determing myocardial damage scores, myocardial injury indicators, myocardial oxidative and inflammatory factors. Western blot analysis was used for cardiac expression of heat shock protein (HSP)72. RESULTS Significant (P less then 0.05) up-regulation of HSP-72 after chronic administration of myricetin coincided with significant (P less then 0.05) reduction in hyperthermia, hypotension, cardiac inflammatory and oxidative damage and lethality. Inhibition of HSP-72 showed a significant (P less then 0.05) reversal in the cardiaprotection as well as survival. CONCLUSIONS Our results indicate that myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72 and show promise as a novel prevention therapeutic for heat stroke. Taxol is a cytotoxic agent against various types of cancers. The cytotoxic activities of Taxol can be extended to its synthesizing plant. Here, Taxol is shown to have special synthesis, storage and transport mechanisms that avoid the toxic effects on its source plant. The sites of Taxol biosynthesis, transport and storage were revealed by quantification of plant Taxol, its intermediate baccatin III, the polyphenol side chain precursor , gene expression analysis of the major Taxol biosynthetic genes and in situ immuno-labeling. Although the biosynthesis of Taxol was limited by the expression of its biosynthetic genes and the presence of baccatin III, its presence did not correlate to baccatin III accumulation, nor to the expression of biosynthetic genes. However, Taxol presence positively correlated to polyphenol accumulation (late stage in Taxol assembly) and the resin-like hydrophobic bodies (HB, storage organelles). These results indicate that the presence of Taxol requires two complementary steps, biosynthesis followed by storage. Each step is limited by the availability of different precursors, which differ in their localization within the plant. Thus, the sites of biosynthesis, transport and storage of Taxol are different. Taxus media (Rehder) plant wood showed high concentrations of baccatin III and the expression of biosynthetic genes. However, the concentrations of Taxol, polyphenol and HB were very high in the plant outer layers including phloem and dead bark (rhytidome). Furthermore, in situ immuno-labeling showed that taxadiene synthase (the rate-limiting enzyme in Taxol biosynthesis) was mainly found in the wood, while Taxol primarily localized to the outer tissues. Conclusively, wood can be considered as the site of Taxol biosynthesis. Our data also propose that Taxol then accumulates into HB in order to permit its transport within the living plant tissues without causing toxic effects. This is followed by Taxol storage in the outer tissues including phloem and dead bark. Psychiatrists are frequently exposed to work-related potential traumatic events (PTEs). A survey was sent to the members of the Dutch Society of Psychiatrists of which 250 questionnaires were eligible for analysis. At least one work-related PTE was reported by 196 (78.4%) of the respondents, of which 177 described the PTE. Witnessing or experiencing verbal aggression (29.2%), physical violence (29.2%) or completed suicide (26.8%) were the most common PTEs. This survey implies that psychiatrists frequently experience work-related PTEs, often with a significant emotional impact. The majority of respondents considered current support as insufficient. Spontaneous theory of mind (ToM) is an unconscious and automatic understanding of others' mental states. Recently, individuals with attention-deficit hyperactivity disorder (ADHD) have been shown to have social and communication difficulties, and ToM in ADHD has come under scrutiny. Although some studies have employed explicit ToM tasks to this end with contradictory results, none, to our knowledge, has investigated spontaneous ToM in individuals with ADHD. Therefore, we performed this study to examine implicit mentalizing in adults with ADHD using the anticipatory-looking paradigm designed by Senju et&nbsp;al. (2009) with a sample of 24 adults with ADHD and 18 neurotypical adults. The total fixation times to three areas of interest, i.e., the actor and the false-belief congruent and incongruent sides of the scene were measured. We found that neither group showed looking bias toward either the false-belief congruent or incongruent side. We interpret that this similar gaze pattern and the absence of looking bias to the false-belief incongruent side in both groups is indicative of intact implicit ToM in adults with ADHD.